scholarly journals MUC5B-Overexpression Induces ER Stress in a Mouse Model of Pulmonary Fibrosis

2020 ◽  
Author(s):  
C. Hennessy ◽  
E. Dobrinskikh ◽  
A.M. Estrella ◽  
J. Michalski ◽  
I.V. Yang ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Mouse Model ◽  
Er Stress

Abstract P118: Inhibition of Endoplasmic Reticulum Stress Prevents Intracranial Aneurysmal Rupture in a Mouse Model

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Daisuke Kudo ◽  
Hajime Furukawa ◽  
Satoru Eguchi ◽  
Tomoki Hashimoto
Keyword(s):  
Endoplasmic Reticulum ◽  
Angiotensin Ii ◽  
Mouse Model ◽  
Er Stress ◽  
Intracranial Aneurysms ◽  
Vehicle Group ◽  
Systemic Hypertension ◽  
Aneurysmal Rupture ◽  
Rupture Rate ◽  
Salt Hypertension

Background: Aneurysmal subarachnoid hemorrhage (SAH) can cause significant mortality and morbidity. To develop a therapy for prevention of intracranial aneurysmal rupture and subsequent SAH, it is important to clarify the mechanism of intracranial aneurysmal rupture. Stimulation of the renin-angiotensin system (RAS) causes hypertension and cardiovascular remodeling. Recent evidence shows that angiotensin II enhances endoplasmic reticulum (ER) stress and inhibition of ER stress prevents angiotensin II-induced vascular remodeling but not hypertension in mice. RAS has also been implicated in intracranial aneurysms. We have previously shown that angiotensin II receptor blocker (losartan) prevented intracranial aneurysmal rupture in a mouse model without affecting systemic hypertension. To clarify the mechanism of intracranial aneurysmal rupture via RAS, we have tested our hypothesis that inhibition of ER stress prevents intracranial aneurysmal rupture in a mouse model. Method: We used a mouse model of intracranial aneurysms in which spontaneous aneurysmal rupture causes neurologic symptoms. Intracranial aneurysms were induced in wild type mice by a single stereotactic injection of elastase (35mU) into the cerebrospinal fluid at right basal cistern and deoxycorticosterone (DOCA)-salt hypertension. Vehicle or 4-phenylbutyric acid (PBA, ER stress inhibitor , 100mg/kg/day) was subcutaneously injected into all mice once a day. To detect aneurysmal rupture, we performed daily neurological examinations. Symptomatic mice were euthanized immediately when they developed neurological symptoms, and all asymptomatic mice were euthanized 21 days after aneurysm induction. The incidence of aneurysms and rupture rate were compared between vehicle group and PBA group. Results: The incidence of aneurysms was not significantly different between two groups (100% in vehicle, 20 of 20 vs. 87% in PBA, 20 of 23, p=0.09). However, rupture rate was significantly lower in the PBA group (60%, 12 of 20) than the vehicle group (95%, 19 of 20). (p=0.008). Conclusion: Inhibition of ER stress reduced aneurysmal rupture in a mouse model of intracranial aneurysm induced by combination of elastase injection and DOCA-salt hypertension.

Amelioration of bleomycin-induced pulmonary fibrosis in a mouse model by a combination therapy of bosentan and imatinib

2015 ◽  
Vol 41 (4) ◽  
pp. 173-188 ◽  
Author(s):  
Shanmuga Reddy Chilakapati ◽  
Mamatha Serasanambati ◽  
Prabhakar Vissavajjhala ◽  
Jagadeeshwara Reddy Kanala ◽  
Damodar Reddy Chilakapati
Keyword(s):  
Pulmonary Fibrosis ◽  
Combination Therapy ◽  
Mouse Model

scholarly journals Protective Effect of Arbidol Against Pulmonary Fibrosis and Sepsis in Mice

2021 ◽  
Vol 11 ◽  
Author(s):  
Hailong Li ◽  
Rui Liu ◽  
Ruotong Zhang ◽  
Shanshan Zhang ◽  
Yiying Wei ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Mouse Model ◽  
Antiviral Drug ◽  
Dynamic Compliance ◽  
Serum Levels ◽  
Inflammatory Factors ◽  
Cytokine Storm ◽  
Viral Immunology ◽  
Sepsis Induction ◽  
Sepsis Score

From the perspective of epidemiology, viral immunology and current clinical research, pulmonary fibrosis may become one of the complications of patients with Coronavirus Disease 2019 (COVID-19). Cytokine storm is a major cause of new coronavirus death. The purpose of this study was to explore the effects of antiviral drug arbidol on cytokine storm and pulmonary fibrosis. Here, we use a mouse model of bleomycin-induced pulmonary fibrosis and a mouse model of fecal dilution-induced sepsis to evaluate the effects of arbidol on pulmonary fibrosis and cytokine storm. The results showed that arbidol significantly reduced the area of pulmonary fibrosis and improved lung function (reduced inspiratory resistance, lung dynamic compliance and forced vital capacity increased). Treatment with arbidol promoted reduced sepsis severity 48 h after sepsis induction, based on weight, murine sepsis score and survival rate. Arbidol observably alleviates inflammatory infiltrates and injury in the lungs and liver. Finally, we also found that arbidol reduced serum levels of pro-inflammatory factors such as TNF-α and IL-6 induced by fecal dilution. In conclusion, our results indicate that arbidol can alleviate the severity of pulmonary fibrosis and sepsis, and provide some reference for the treatment of cytokine storm and sequelae of pulmonary fibrosis in patients with COVID-19.

scholarly journals IL-1 receptor blockade skews inflammation towards Th2 in a mouse model of systemic sclerosis

2019 ◽  
Vol 54 (3) ◽  
pp. 1900154 ◽  
Author(s):  
Anna Birnhuber ◽  
Slaven Crnkovic ◽  
Valentina Biasin ◽  
Leigh M. Marsh ◽  
Balazs Odler ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Lung Function ◽  
Pulmonary Fibrosis ◽  
Mouse Model ◽  
Molecular Mechanisms ◽  
Pulmonary Involvement ◽  
Specific Patient ◽  
Alternatively Activated Macrophages ◽  
Alternatively Activated

The interleukin (IL)-1 family of cytokines is strongly associated with systemic sclerosis (SSc) and pulmonary involvement, but the molecular mechanisms are poorly understood. The aim of this study was to assess the role of IL-1α and IL-1β in pulmonary vascular and interstitial remodelling in a mouse model of SSc.IL-1α and IL-1β were localised in lungs of SSc patients and in the fos-related antigen-2 (Fra-2) transgenic (TG) mouse model of SSc. Lung function, haemodynamic parameters and pulmonary inflammation were measured in Fra-2 TG mice with or without 8 weeks of treatment with the IL-1 receptor antagonist anakinra (25 mg·kg−1·day−1). Direct effects of IL-1 on pulmonary arterial smooth muscle cells (PASMCs) and parenchymal fibroblasts were investigated in vitro.Fra-2 TG mice exhibited increased collagen deposition in the lung, restrictive lung function and enhanced muscularisation of the vasculature with concomitant pulmonary hypertension reminiscent of the changes in SSc patients. Immunoreactivity of IL-1α and IL-1β was increased in Fra-2 TG mice and in patients with SSc. IL-1 stimulation reduced collagen expression in PASMCs and parenchymal fibroblasts via distinct signalling pathways. Blocking IL-1 signalling in Fra-2 TG worsened pulmonary fibrosis and restriction, enhanced T-helper cell type 2 (Th2) inflammation, and increased the number of pro-fibrotic, alternatively activated macrophages.Our data suggest that blocking IL-1 signalling as currently investigated in several clinical studies might aggravate pulmonary fibrosis in specific patient subsets due to Th2 skewing of immune responses and formation of alternatively activated pro-fibrogenic macrophages.

The effect of H19-miR-29b interaction on bleomycin-induced mouse model of idiopathic pulmonary fibrosis

2016 ◽  
Vol 479 (3) ◽  
pp. 417-423 ◽  
Author(s):  
Yongjun Tang ◽  
Ruoxi He ◽  
Jian An ◽  
Pengbo Deng ◽  
Li Huang ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Mouse Model

Muc5b-Overexpression Promotes Increased ER Stress in Mouse Models of Pulmonary Fibrosis

2019 ◽  
Author(s):  
J.E. Michalski ◽  
A.M. Estrella ◽  
C.E. Hennessy ◽  
I.T. Stancil ◽  
E. Dobrinskikh ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Er Stress ◽  
Mouse Models

scholarly journals The Effects of Lung-Moistening Herbal Medicines on Bleomycin-Induced Pulmonary Fibrosis Mouse Model

Processes ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 102
Author(s):  
Junmo Ahn ◽  
Hyejin Joo ◽  
Jihye Park ◽  
Jae-Woo Park ◽  
Kwan-Il Kim ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Pulmonary Fibrosis ◽  
Mouse Model ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Herbal Medicines ◽  
Intratracheal Instillation ◽  
Lavage Fluid ◽  
Septal Thickness ◽  
Different Doses

In traditional medicine, lung-moistening herbal medicines (LMHM) are regarded as a major option for treating symptoms of pulmonary fibrosis (PF) including dry cough and dyspnea. As PF agents are being applied to the development of lung cancer agents, PF and lung cancer are reported to have high pathological and pharmacological relationships. This study was proposed to identify candidates for the treatment of PF via investigating the effect of LMHM on PF mouse model. PF was induced by intratracheal instillation of bleomycin. Six water extracts of LMHM such as Farfarae Flos (FAF), Trichosanthis Semen (TRS), Lilii Bulbus (LIB), Adenophorae Radix (ADR), Asteris Radix (ASR), and Scrophulariae Radix (SCR) were prepared and administered (300 mg/kg) orally for 10 days after induction. The changes in body weight, histopathology, and immune cell of bronchoalveolar lavage fluid (BALF) were investigated. Among those, LIB and ADR significantly decreased the deposition of collagen and septal thickness of alveolar and terminal bronchiole. Moreover, SCR, TRS, LIB, and ADR decreased total cells, macrophages, and lymphocytes in BALF. Taken together, ADR and LIB could be the candidates to reduce PF. Further studies on their effects at different doses and analysis of their underlying molecular mechanisms are needed.

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